Newsletter Xagena

Hepatitis C: new regimens with direct acting antivirals

The approval of two hepatitis C virus ( HCV ) protease inhibitors by the FDA ( Food and Drug Administration ) in 2011, Boceprevir ( Victrelis ) and Telaprevir ( Incivo, Incivek ), marked the start of a new chapter in hepatitis C treatment.
These were the first new drugs approved in 10 years for hepatitis C treatment.

With Boceprevir and Telaprevir, triple combination therapy for patients with genotype 1 HCV infection became available, combining Peginterferon and Ribavirin with either of these two agents. This represented a huge advance in hepatitis C treatment, with improved sustained viral response ( SVR ) rates among patients who had never been treated before as well as among patients who had relapsed after treatment or did not fully respond to standard treatment.

But the story of hepatitis C treatment did not end here. Multiple other drugs were also developed for all strains of HCV, not just genotype 1.

In 2013, the FDA approved two more drugs, Sofosbuvir ( Sovaldi ) and Simeprevir ( Olysio ). Sofosbuvir represented the first approved drug for use as an all oral regimen, in combination with Ribavirin, and marked a very significant new era for hepatitis C patients who had not been eligible for treatment previously due to interferon contraindications. It is anticipated that several other new agents and combinations of agents may be approved in 2014-2015, making several new treatment regimens available for patients.

Many DAAs have been showing phase 2 and phase 3 trials with increased SVR rates, shortened durations of treatment, and acceptable adverse event profiles, creating intriguing possibilities for patients who have not been candidates for hepatitis C treatment because of the toxicities caused by Interferon. But, it is also important to know that these results have been obtained in carefully selected clinical trial populations and that effectiveness in the real-world is unlikely to be as high. In addition, the relatively small numbers of patients treated in these trials mean that these new drugs may show unexpected side effects.

Clinical trials

The following are summaries of some of the key reported clinical trials of newly-approved and investigational HCV agents.

FUSION: phase 3 trial of Sofosbuvir / Ribavirin in treatment experienced for 12 weeks in genotype 2/3 patients with an 86% SVR12 in genotype 2 and a 30% SVR12 in genotype 3 patients. For 16 weeks, there was a 94% SVR12 in genotype 2 and a 62% SVR12 in genotype 3;

ELECTRON: phase 2 trial of 12 weeks of Sofosbuvir and Ledipasvir plus Ribavirin for varying durations in genotype 1; SVR12 in 100% of treatment-naive patients, and SVR 12 of 100% in prior null-responders from past treatment-experience;

LONESTAR: phase 2 trial of a fixed-dose combination of Sofosbuvir / Ledipasvir, with or without Ribavirin for varying durations in genotype 1; SVR12 of 100% in treatment-naive patients for 8 weeks of treatment including Ribavirin, and SVR4 of 95% in patients failing prior treatment with protease inhibitors treated for 12 weeks;